1. Field of The Invention
This invention variously relates to contrast agents for X-ray imaging, a method of imaging a visualizable corporeal situs by radiological imaging techniques (comprising delivery to the situs of an imagingly effective amount of an imagingly effective, physiologically acceptable contrast agent), and contrast media formulations useful for such imaging.
2. Description of the Related Art
In fields such as angiography, urography, and gynecology, as well as in other medical diagnostic and treatment fields, radiological imaging reagents are employed. These reagents comprise contrast agents which typically are administered in compositions or formulations to the patient or subject, for delivery to the corporeal situs part of the body) to be visualized. After administration to the body, the corporeal region to be visualized is subjected to radiation (e.g., X-ray) exposure and fluoroscopic analysis.
By way of example, radiological reagents (sometimes hereinafter referred to as "contrast agents", "contrast media", "contrast media reagents", or "imaging reagents") are delivered to a coronary situs in coronary angioplasty by means of an angiographic syringe or injector, which directs the contrast media through a catheter or other passage means into the appropriate coronary lumen. Stenosis due to vascular plaques are similarly visualized by catheter-mediated introduction of contrast medium to the vascular lumen, in connection with potential use of arterial angioplasty techniques (e.g., balloon angioplasty or laser angioplasty), by means of which the vascular plaque is treated to deocclude the arterial lumen. In gynecological diagnosis, an imaging reagent may be transcervically introduced by a syringe, pump, or injector, following which the pelvic region is radiologically visualized.
Contrast media reagents comprise a constituent imparting radiopacity thereto, typically an iodine-based compound which is physiologically acceptable, e.g., organically-bound iodine. Examples of commercially available iodine-based radiological imaging reagents include the iodine-based radiopaque contrast medium formulation which is commercially available under the trademark VASCORAY.RTM. from Mallinckrodt Corporation (St. Louis, Mo., USA).
X-ray contrast agents already known in the art include a number of halogenated derivatives, especially iodinated derivatives, of 5-amino-isophthalic acid, e.g., the halogenated derivatives described in French Patent No. 2 053 037.
While commercially available imaging formulations are of generally effective and useful character, they nonetheless have some limiting and sub-optimal characteristics attendant their use.
The contrast medium must be completely removed (flushed, or otherwise extracted) from the corporeal system following visualization of the desired situs.
The active ingredient of conventional iodine-based imaging formulations frequently has a relatively low concentration or "loading" of iodine associated therewith, as a result of which relatively high dosages of the contrast medium are required.
In addition, the active ingredients employed in many radiological imaging formulations frequently are poorly soluble in the carrier medium of the formulation.
Further, many of the X-ray contrast agents in commercial use have undesirable toxicity, osmolality, viscosity, and cost characteristics.
Accordingly, it would be an advance in the art to provide a superior radiological imaging reagent which (1) is physiologically acceptable, (2) is safe, highly effective, and efficient in character, e.g., at relatively low dosage, (3) comprises an active ingredient which is water soluble so that water may be employed as the solvent medium of the reagent formulation, (4) is excreted in normal functioning of the corporeal system, and (5) produces (aqueous) formulations characterized by low osmolality and low viscosity.
Relative to the contrast agents, radiological visualizing method, and contrast media formulations of the present invention, relevant art comprises the aforementioned French Patent 2 053 037 and the art which is described below.
U.S. Pat. No. 4,847,065 to A. Y. Akimova et al discloses iodine-containing radiopaque organic acids, as described at column 3, lines 15-21 of the patent.
U.S. Pat. No. 4,713,235 to R. E. Krall discloses organic iodo agents, particularly iodo carboxylic acids, as radiopaque agents in acrylate-based occlusion compositions for female sterilization. The iodine reagents are discussed at column 3, line 20 to column 4, line 22 of the patent.
As mentioned above, a diagnostic radiopaque formulation is commercially available from Mallinckrodt, Inc. (St. Louis, Mo.) under the trademark VASCORAY.RTM.. This contrast media formulation is a phosphate-buffered solution containing organically bound iodine.
Commercially available diagnostic radiopaque media are variously used in aortography, angiocardiography, and excretory urography.